CA2942533C - Modulateurs allosteriques des proteines du noyau de l'hepatite b - Google Patents
Modulateurs allosteriques des proteines du noyau de l'hepatite b Download PDFInfo
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- CA2942533C CA2942533C CA2942533A CA2942533A CA2942533C CA 2942533 C CA2942533 C CA 2942533C CA 2942533 A CA2942533 A CA 2942533A CA 2942533 A CA2942533 A CA 2942533A CA 2942533 C CA2942533 C CA 2942533C
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- 125000001424 substituent group Chemical group 0.000 claims description 71
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- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 92
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- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 54
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 49
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 42
- 101150041968 CDC13 gene Proteins 0.000 description 40
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 40
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- 239000006188 syrup Substances 0.000 description 38
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 29
- 239000000543 intermediate Substances 0.000 description 29
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 28
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- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 25
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- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 21
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
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- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 12
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Classifications
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
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- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
- C07D223/20—Dibenz [b, e] azepines; Hydrogenated dibenz [b, e] azepines
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/38—[b, e]- or [b, f]-condensed with six-membered rings
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- C—CHEMISTRY; METALLURGY
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- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
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- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D281/14—[b, e]-condensed
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
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- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D281/16—[b, f]-condensed
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
La présente invention concerne, en partie, des composés ayant des propriétés d'effecteurs allostériques contre les protéines du noyau du virus de l'hépatite B. L'invention concerne également des procédés de traitement d'infections virales, telles que l'hépatite B, consistant à administrer un composé selon l'invention à un patient nécessitant un tel traitement.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201461952467P | 2014-03-13 | 2014-03-13 | |
US61/952,467 | 2014-03-13 | ||
US201462010025P | 2014-06-10 | 2014-06-10 | |
US62/010,025 | 2014-06-10 | ||
PCT/US2015/020444 WO2015138895A1 (fr) | 2014-03-13 | 2015-03-13 | Modulateurs allostériques des protéines du noyau de l'hépatite b |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2942533A1 CA2942533A1 (fr) | 2015-09-17 |
CA2942533C true CA2942533C (fr) | 2020-12-08 |
Family
ID=54072461
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CA2942533A Active CA2942533C (fr) | 2014-03-13 | 2015-03-13 | Modulateurs allosteriques des proteines du noyau de l'hepatite b |
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EP (3) | EP3607950A3 (fr) |
JP (2) | JP6602311B2 (fr) |
KR (1) | KR102363174B1 (fr) |
CN (2) | CN110437153A (fr) |
AP (1) | AP2016009477A0 (fr) |
AU (2) | AU2015229174B2 (fr) |
CA (1) | CA2942533C (fr) |
CL (1) | CL2016002269A1 (fr) |
DK (1) | DK3116316T3 (fr) |
DO (1) | DOP2016000233A (fr) |
ES (1) | ES2748029T3 (fr) |
HR (1) | HRP20191444T1 (fr) |
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SG (2) | SG10202001506UA (fr) |
WO (1) | WO2015138895A1 (fr) |
ZA (1) | ZA201606209B (fr) |
Families Citing this family (61)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI519515B (zh) | 2011-12-21 | 2016-02-01 | 諾維拉治療公司 | B型肝炎抗病毒劑 |
SG11201501359TA (en) | 2012-08-28 | 2015-03-30 | Janssen Sciences Ireland Uc | Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of hepatitis b |
EA027194B1 (ru) | 2013-02-28 | 2017-06-30 | Янссен Сайенсиз Айрлэнд Юси | Сульфамоил-ариламиды и их применение в качестве лекарственных препаратов для лечения гепатита b |
EP2981536B1 (fr) | 2013-04-03 | 2017-06-14 | Janssen Sciences Ireland UC | Dérivés de n-phenyl-carboxamide et leur utilisation comme médicaments pour le traitement de l'hépatite b |
JO3603B1 (ar) | 2013-05-17 | 2020-07-05 | Janssen Sciences Ireland Uc | مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي |
AU2014267235B2 (en) | 2013-05-17 | 2017-10-05 | Janssen Sciences Ireland Uc | Sulphamoylthiophenamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
HUE039152T2 (hu) | 2013-07-25 | 2018-12-28 | Janssen Sciences Ireland Uc | Glioxamiddal szubsztituált pirrolamid-származékok és alkalmazásuk hepatitisz B kezelésére szolgáló gyógyszerként |
AP2016009122A0 (en) | 2013-10-23 | 2016-03-31 | Janssen Sciences Ireland Uc | Carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
US10392349B2 (en) | 2014-01-16 | 2019-08-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
MX2016009449A (es) | 2014-02-05 | 2016-10-13 | Novira Therapeutics Inc | Terapia de combinacion para el tratamiento de infecciones por virus de la hepatitis b (vhb). |
US11078193B2 (en) | 2014-02-06 | 2021-08-03 | Janssen Sciences Ireland Uc | Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
RS59430B1 (sr) | 2014-03-13 | 2019-11-29 | Univ Indiana Res & Tech Corp | Alosterni modulatori proteina jezgra hepatitisa b |
JP2018510159A (ja) | 2015-03-19 | 2018-04-12 | ノヴィラ・セラピューティクス・インコーポレイテッド | アゾカン及びアゾナン誘導体及びb型肝炎感染症の治療法 |
US10875876B2 (en) | 2015-07-02 | 2020-12-29 | Janssen Sciences Ireland Uc | Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
JP6993318B2 (ja) * | 2015-07-15 | 2022-02-03 | エージェンシー フォー サイエンス,テクノロジー アンド リサーチ | B型肝炎ウイルス複製の調節 |
TWI721016B (zh) * | 2015-09-15 | 2021-03-11 | 美商艾森伯利生物科學公司 | B型肝炎核心蛋白質調節劑 |
WO2017059059A1 (fr) | 2015-09-29 | 2017-04-06 | Novira Therapeutics, Inc. | Formes cristallines d'un agent antiviral de l'hépatite b |
WO2017181141A2 (fr) | 2016-04-15 | 2017-10-19 | Novira Therapeutics, Inc. | Associations et méthodes comprenant un inhibiteur d'ensemble capside |
EP3455219A4 (fr) | 2016-05-10 | 2019-12-18 | C4 Therapeutics, Inc. | Dégronimères de c3-glutarimide liés à une amine pour la dégradation de protéines cibles |
EP4491236A2 (fr) | 2016-05-10 | 2025-01-15 | C4 Therapeutics, Inc. | Dégronimères hétérocycliques pour la dégradation de protéines cibles |
WO2017197036A1 (fr) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | Dégronimères spirocycliques pour la dégradation de protéines cibles |
WO2017197046A1 (fr) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | Dégronimères de type glutarimide liés au carbone c3 pour la dégradation de protéines cibles |
CA3037151A1 (fr) * | 2016-09-15 | 2018-03-22 | Assembly Biosciences, Inc. | Modulateurs des proteines du noyau de l'hepatite b |
EP3519399A1 (fr) * | 2016-10-03 | 2019-08-07 | Sigilon Therapeutics, Inc. | Composés, dispositifs et utilisations associées |
SG11201902944TA (en) | 2016-11-07 | 2019-05-30 | Arbutus Biopharma Corp | Substituted pyridinone-containing tricyclic compounds, and methods using same |
CN106632177A (zh) * | 2016-12-05 | 2017-05-10 | 万特制药(海南)有限公司 | 雷美替胺中间体的制备方法 |
SG11201907725SA (en) | 2017-02-23 | 2019-09-27 | Fujian Cosunter Pharmaceutical Co Ltd | Tri-cycle compound and applications thereof |
ES2898217T3 (es) | 2017-03-02 | 2022-03-04 | Assembly Biosciences Inc | Compuestos de sulfamida cíclica y métodos de uso de los mismos |
KR102575605B1 (ko) * | 2017-03-13 | 2023-09-05 | 어셈블리 바이오사이언시스, 인크. | B형 간염 코어 단백질 조정제의 제조 방법 |
WO2018172852A1 (fr) | 2017-03-21 | 2018-09-27 | Arbutus Biopharma Corporation | Dihydroindène-4-carboxamides substitués, leurs analogues et procédés d'utilisation correspondant |
AU2018304907B2 (en) | 2017-07-21 | 2022-11-24 | Antabio Sas | Chemical compounds |
EP3704119A1 (fr) | 2017-11-02 | 2020-09-09 | AiCuris GmbH & Co. KG | Nouveaux indole-2-carboxamides à substitution pyrazolo-pipéridine hautement actifs agissant contre le virus de l'hépatite b (vhb) |
BR112020008762A2 (pt) | 2017-11-02 | 2020-10-20 | Aicuris Gmbh & Co. Kg | indol-2-carboxamidas amino-tiazol substituídas altamente ativas inovadoras ativas contra o vírus da hepatite b (hbv) |
JP2021515769A (ja) | 2018-03-14 | 2021-06-24 | ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー | カプシド集合調節剤の投薬レジメン |
IL278460B1 (en) * | 2018-05-03 | 2024-12-01 | Univ Emory | Modulators of orphan nuclear receptors for nash and other metabolic disorders |
CN110627752B (zh) * | 2018-06-25 | 2021-08-17 | 新发药业有限公司 | 一种3-氨甲基四氢呋喃的制备方法 |
CN108863884B (zh) * | 2018-07-26 | 2020-07-03 | 南京富润凯德生物医药有限公司 | 一种用dast试剂作为消除试剂合成共轭硝基烯取代系列衍生物的方法 |
TWI826492B (zh) | 2018-07-27 | 2023-12-21 | 加拿大商愛彼特生物製藥公司 | 經取代四氫環戊[c]吡咯、經取代二氫吡咯,其類似物及使用其之方法 |
JP7118354B2 (ja) | 2018-08-23 | 2022-08-16 | 福建▲広▼生中霖生物科技有限公司 | 三環式化合物の結晶形及びその使用 |
AR116946A1 (es) | 2018-11-02 | 2021-06-30 | Aicuris Gmbh & Co Kg | Derivados de urea 6,7-dihidro-4h-pirazolo[4,3-c]piridinas activas contra el virus de la hepatitis b (vhb) |
UY38434A (es) | 2018-11-02 | 2020-05-29 | Aicuris Gmbh & Co Kg | Nuevas 6,7-dihidro-4h-pirazolo[1,5-a]pirazin indol-2-carboxamidas activas contra el virus de la hepatitis b (hbv) |
UY38437A (es) | 2018-11-02 | 2020-05-29 | Aicuris Gmbh & Co Kg | Nuevas urea 6,7-dihidro-4h-pirazolo[1,5-a]pirazinas activas contra el virus de la hepatitis b (hbv) |
UY38435A (es) | 2018-11-02 | 2020-05-29 | Aicuris Gmbh & Co Kg | Nuevas urea 6,7-dihidro-4h-pirazol[1,5-a] pirazinas activas contra el virus de la hepatitis b (vhb) |
UY38436A (es) | 2018-11-02 | 2020-05-29 | Aicuris Gmbh & Co Kg | Nuevas 6,7-dihidro-4h-pirazolo[1,5-a] pirazinindol-2-carboxamidas activas contra el virus de la hepatitis b (vhb) |
TW202415643A (zh) | 2018-12-12 | 2024-04-16 | 加拿大商愛彼特生物製藥公司 | 經取代之芳基甲基脲類及雜芳基甲基脲類、其類似物及其使用方法 |
EP3897631A4 (fr) | 2018-12-20 | 2022-11-23 | C4 Therapeutics, Inc. | Dégradation ciblée de protéines |
EP3927698A1 (fr) | 2019-02-22 | 2021-12-29 | Janssen Sciences Ireland Unlimited Company | Dérivés d'amide utiles dans le traitement d'une infection par le virus de l'hépatite b ou de maladies induites par le virus de l'hépatite b |
KR20220002498A (ko) | 2019-04-30 | 2022-01-06 | 아이쿠리스 게엠베하 운트 코. 카게 | B형 간염 바이러스 (hbv)에 대해 활성인 신규 인돌리진-2-카르복스아미드 |
KR20220002499A (ko) | 2019-04-30 | 2022-01-06 | 아이쿠리스 게엠베하 운트 코. 카게 | B형 간염 바이러스 (hbv)에 대해 활성인 신규 페닐 및 피리딜 우레아 |
KR20220003023A (ko) | 2019-04-30 | 2022-01-07 | 아이쿠리스 게엠베하 운트 코. 카게 | B형 간염 바이러스 (hbv)에 대해 활성인 신규 옥살릴 피페라진 |
JP2022530522A (ja) | 2019-04-30 | 2022-06-29 | アイクリス ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト | B型肝炎ウイルス(hbv)に対し活性な新規のインドール-2-カルボキサミド |
US11491148B2 (en) | 2019-05-06 | 2022-11-08 | Janssen Sciences Ireland Unlimited Company | Amide derivatives useful in the treatment of HBV infection or HBV-induced diseases |
KR20220043931A (ko) * | 2019-05-24 | 2022-04-05 | 어셈블리 바이오사이언시스, 인크. | Hbv의 치료를 위한 제약 조성물 |
CN110526878A (zh) * | 2019-09-16 | 2019-12-03 | 成都睿智化学研究有限公司 | 一种2-(噁唑基)乙胺的制备方法 |
CN111072551A (zh) * | 2019-12-30 | 2020-04-28 | 上海睿瓦科技有限公司 | 催化氢化一步法制取哌啶胺的方法 |
IL297305A (en) * | 2020-04-22 | 2022-12-01 | Assembly Biosciences Inc | The heteroaryl carboxamide compounds of pentadentate compounds for the treatment of HBV |
CN113135848A (zh) * | 2021-04-26 | 2021-07-20 | 深圳市华先医药科技有限公司 | 一种巯基烯酯类化合物的制备方法 |
CN113636960A (zh) * | 2021-08-24 | 2021-11-12 | 上海皓元医药股份有限公司 | 一种2-(氯磺酰基)环己烷-1-烯甲酸乙酯衍生物的制备方法 |
CN113717080A (zh) * | 2021-10-09 | 2021-11-30 | 西安瑞联新材料股份有限公司 | 一种4-氯-2-氰基苯磺酰氯的合成方法 |
WO2024089216A1 (fr) | 2022-10-27 | 2024-05-02 | Syngenta Crop Protection Ag | Nouveaux composés hétéroaryl-carboxamides contenant du soufre |
Family Cites Families (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1480553A (en) * | 1976-06-03 | 1977-07-20 | Pfizer Ltd | Tricyclic sulphonamides |
JPS58225074A (ja) | 1982-06-25 | 1983-12-27 | Chugai Pharmaceut Co Ltd | ジベンゾオキサゼピン誘導体 |
GB9109557D0 (en) * | 1991-05-02 | 1991-06-26 | Wellcome Found | Chemical compounds |
US5512563A (en) | 1993-07-29 | 1996-04-30 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
CA2542064A1 (fr) * | 2003-10-24 | 2005-05-06 | Exelixis, Inc. | Modulateurs de kinases tao et leurs methodes d'utilisation |
DE102004004928A1 (de) * | 2004-01-31 | 2005-08-18 | Bayer Healthcare Ag | Dibenzoxazepine II |
WO2007047737A1 (fr) * | 2005-10-17 | 2007-04-26 | Acadia Pharmaceuticals Inc. | Composes modulateurs de cb-1 et leur utilisation |
WO2007056388A2 (fr) | 2005-11-07 | 2007-05-18 | The General Hospital Corporation | Compositions et procédés de modulation de l’activité de la poly(adp-ribose) polymérase |
US20100022509A1 (en) | 2006-06-07 | 2010-01-28 | Fahey Robert C | Inhibitors of MshC and Homologs Thereof, and Methods of Identifying Same |
WO2008118141A2 (fr) | 2006-10-17 | 2008-10-02 | Acadia Pharmaceuticals Inc. | Utilisation de composés de modulation des cannabinoïdes en association avec d'autres composés thérapeutiques comme traitement d'appoint |
CN102164605A (zh) * | 2008-07-23 | 2011-08-24 | 美国卫生和人力服务部 | 用作抗疟药的疟原虫表面阴离子通道抑制剂 |
WO2011075607A1 (fr) * | 2009-12-18 | 2011-06-23 | Intermune, Inc. | Nouveaux inhibiteurs de la réplication du virus de l'hépatite c |
WO2012045194A1 (fr) | 2010-10-09 | 2012-04-12 | Abbott Laboratories | Benzodiazépinones à titre d'inhibiteurs de fak pour le traitement du cancer |
CN103889953B (zh) | 2011-07-01 | 2016-06-08 | 巴鲁﹒S﹒布隆伯格研究所 | 作为防乙型肝炎病毒感染的抗病毒剂的氨磺酰苯甲酰胺衍生物 |
WO2013010069A1 (fr) | 2011-07-13 | 2013-01-17 | Indiana University Research And Technology Corporation | Protéine structurale virale modifiée ayant une activité antivirale |
EA026977B1 (ru) | 2012-01-06 | 2017-06-30 | Янссен Сайенсиз Айрлэнд Юси | 4,4-дизамещенные 1,4-дигидропиримидины и их применение в качестве лекарственных препаратов для лечения гепатита b |
NZ704758A (en) | 2012-08-28 | 2018-06-29 | Janssen Sciences Ireland Uc | Fused bicyclic sulfamoyl derivatives and the use thereof as medicaments for the treatment of hepatitis b |
SG11201501359TA (en) | 2012-08-28 | 2015-03-30 | Janssen Sciences Ireland Uc | Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of hepatitis b |
KR20150054795A (ko) | 2012-09-10 | 2015-05-20 | 에프. 호프만-라 로슈 아게 | B형 간염 바이러스 감염의 치료 및 예방을 위한 6-아미노산 헤테로아릴다이하이드로피리미딘 |
BR112015010461A2 (pt) | 2012-11-09 | 2017-07-11 | Univ Indiana Res & Tech Corp | usos alternativos para efetores da reunião do hbv |
CN110642741A (zh) | 2012-12-06 | 2020-01-03 | 巴鲁克斯布隆伯格研究所 | 作为抗hbv感染的抗病毒剂的官能化苯甲酰胺衍生物 |
JP6409001B2 (ja) | 2012-12-27 | 2018-10-17 | ドレクセル ユニバーシティ | Hbv感染に対する新規抗ウイルス剤 |
RU2519546C1 (ru) | 2013-01-16 | 2014-06-10 | Общество С Ограниченной Ответственностью "Биоинтегратор" (Ооо "Биоинтегратор") | КОНЪЮГАТЫ И МАЛЫЕ МОЛЕКУЛЫ, ВЗАИМОДЕЙСТВУЮЩИЕ С РЕЦЕПТОРОМ CD16а |
EA027194B1 (ru) | 2013-02-28 | 2017-06-30 | Янссен Сайенсиз Айрлэнд Юси | Сульфамоил-ариламиды и их применение в качестве лекарственных препаратов для лечения гепатита b |
AR095426A1 (es) | 2013-03-14 | 2015-10-14 | Onyx Therapeutics Inc | Inhibidores tripeptídicos de la epoxicetona proteasa |
KR102350704B1 (ko) | 2013-03-15 | 2022-01-13 | 셀젠 카르 엘엘씨 | 헤테로아릴 화합물 및 이의 용도 |
EP2981536B1 (fr) | 2013-04-03 | 2017-06-14 | Janssen Sciences Ireland UC | Dérivés de n-phenyl-carboxamide et leur utilisation comme médicaments pour le traitement de l'hépatite b |
JO3603B1 (ar) | 2013-05-17 | 2020-07-05 | Janssen Sciences Ireland Uc | مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي |
CA2911214A1 (fr) | 2013-05-17 | 2014-11-20 | F. Hoffmann-La Roche Ag | Heteroaryldihydropyrimidines pontees en position 6 pour le traitement et la prophylaxie d'une infection par le virus de l'hepatite b |
AU2014267235B2 (en) | 2013-05-17 | 2017-10-05 | Janssen Sciences Ireland Uc | Sulphamoylthiophenamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
SG11201509508YA (en) | 2013-06-19 | 2015-12-30 | Seragon Pharmaceuticals Inc | Estrogen receptor modulator and uses thereof |
US9550742B2 (en) | 2013-07-29 | 2017-01-24 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | 11-OXO-10,11-dihydrodibenzo[B,F][1,4]thiazepine S-oxide derivatives and their use as dopamine D2 receptor antagonists |
RS59430B1 (sr) | 2014-03-13 | 2019-11-29 | Univ Indiana Res & Tech Corp | Alosterni modulatori proteina jezgra hepatitisa b |
MX2016016405A (es) | 2014-06-10 | 2017-04-06 | Basf Se | Compuestos de [1,2,4]triazol e imidazol sustituidos como fungicidas. |
TWI721016B (zh) | 2015-09-15 | 2021-03-11 | 美商艾森伯利生物科學公司 | B型肝炎核心蛋白質調節劑 |
US10811219B2 (en) | 2018-08-07 | 2020-10-20 | Applied Materials Israel Ltd. | Method for evaluating a region of an object |
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Effective date: 20180319 |